PB2182: NEUTROPHIL TO LYMPHOCYTE RATIO (NLR) AT DIAGNOSIS IN ESSENTIAL THROMBOCYTEMIA (ET): A NEW PREDICTOR OF THROMBOTIC EVENTS
Authors: Alessia Ripamonti, Fabrizio Cavalca, Elena Agostani, Carlo Gambacorti-Passerini, Elena Maria Elli
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Myeloproliferative neoplasms (MPNs) are characterized by dysregulation in JAK-STAT pathway that determine the clonal expansion of one or more blood cell lineages. In addition to these intracellular changes in the malignant clone, inflammatory processes involving both the clonal and the non-clonal cells contribute to the signs and symptoms of the patients (pts), as well as to progression of the disease to myelofibrosis (MF) or acute leukemia, and to thrombotic complications. Neutrophil-to-lymphocyte ratio (NLR) reflects the imbalance between systemic inflammation and immunity and is emerging as a prognostic biomarker in several diseases, including hematological ones. Aims: We analyzed retrospectively in a cohort of patients with ET the relationship between NLR value at diagnosis and the risk of thrombotic events, disease progression into MF and overall survival (OS). Methods: A total of 473 pts with diagnosis of ET according to current WHO guidelines, followed in San Gerardo Hospital, were enrolled in the INFLA-ME (INFLAmmation in myeloproliferativE disease) trial between 1995 and 2022. Clinical, histopathological, and hematological data were collected retrospectively. NLR value was calculated as the ratio between absolute neutrophil count (ANC) and lymphocyte count (ALC) at diagnosis. Pts were dichotomized using the best threshold of NLR identified by ROC analysis. Thrombotic complications included both arterial (ischemic stroke, myocardial infarction, peripheral arterial disease) and venous (deep vein thrombosis, pulmonary embolism, cerebral and splanchnic vein thrombosis) events. Thrombosis-free survival (TFS) and OS were determined from ET diagnosis to the first thrombotic event and to death or last contact, respectively. Results: Overall, 473 pts were included in the study. Median age at diagnosis was 64.7 years (range: 18-92), Ratio F/M was 1.62. Most of pts was JAK2 V617F mutated (69%) and 372 pts (78%) were classified as intermediate-high IPSET score. We reported 73 thrombotic events (47 arterial and 26 venous) in 14.5% pts (69) for an incidence rate of 1.7 x 100 pts/year. By ROC analysis, 4 was identified as the best cut-off value to dichotomize pts based on NLR. In statistical analysis, age ≥ 65 years (p=0.04), IPSET score intermediate-high (p=0.03), prior/at diagnosis thrombosis (p<0.0001) were associated with a significant risk of thrombotic events. CALR mutation was protective against thrombotic events (p=0.02). NLR value ≥ 4 at diagnosis was associated with higher thrombotic risk (p<0.0001, both arterial (p<0.0001) and venous (p=0.02) with a shorter TFS compared with NLR < 4 (p<0.0001, Fig. 1). With a median follow-up of 7.8 years (range: 0.6-21), 48 pts progressed to MF (10%). A total of 77 pts died (16,2%), 13 of them (16,8%) for evolution into acute leukemia. NLR value ≥ 4 was not associated with evolution to MF and OS. Summary/Conclusion: NLR, a simple, cost-effective and easy to obtain inflammatory marker can predict at diagnosis the risk of thrombosis in ET. We first found that pts with NLR value ≥ 4 have a significant higher risk of thrombotic events, both arterial and venous. Despite the retrospective nature of the study, these data are promising but require to be validated in larger and prospective studies.Keywords: Essential Thrombocytemia, Thrombosis